OBJECTIVES: During the variable but often extended period between determination of HIV seropositivity and diagnosis of AIDS, emotional distress is common and some people become clinically depressed. The questions we address are whether depression in the context of HIV infection can be alleviated by imipramine, and whether the medication itself alters immune status. Since HIV infection and knowledge of such infection themselves constitute stressors, the issue is whether such stress-induced depression should be treated with psychotropic medication. Positive clinical findings will contradict the common attitude that depression after HIV infection is only natural and therefore its treatment is irrelevant. A secondary question is whether alleviation of depression is associated with an increase in health-promoting behavior. Such findings would have positive public health implications. METHOD: We propose a six-week double-blind placebo controlled trial imipramine, followed by 4 1/2 months of open treatment. Our object is to determine whether imipramine is superior to placebo in treating DSM-III-R major depression in HIV+ gay men with absent to moderate HIV symptoms at study baseline. Assessment of major study variables will be done at baseline and at Weeks 6, 12 and 26. Over three years we expect 80 study completers at Week 6. In addition, we will include a small number of men who are otherwise study eligible but who are HIV- or who have not been tested, to protect confidentiality of study participants. We also will ascertain whether imipramine affects immune status as measured by T cell subsets, p24 antigen test and acid-labile alpha interferon test. These will be assessed at baseline and Weeks 12 and 26. T cell subsets will be assessed at Week 6 as well. With anticipated attrition after Week 6, we expect to have Week 26 measures for at least 60 patients over a three-year period. For baseline-Week 26 analyses, we will draw two additional comparison groups from a longitudinal naturalistic study of a community sample of 120 gay men now being conducted in our Department's HIV Center.